Summary

Findings from a recent study suggest that earlier start of
treatment with factor VIII in patients with severe hemophilia is
associated with a higher risk to develop inhibitors.
We set out to assess the association between age of first
administration of clotting factor VIII and the risk to develop
inhibitors in infants with severe hemophilia A.
This work was a cohort study, carried out in the national
hemophilia treatment center. The study included eighty-one
consecutive patients with severe hemophilia A who received
their first dose of factor VIII between 1975 and 1998. Patients
were followed until their last visit in 2001 or 2002.
The average follow-up was 16 years (range 3-26). Persistent
inhibitory antibodies developed in 12 of 81 patients (15%).
Cumulative incidence at 100 exposure days was 34% (95%
confidence interval 7-61%) in patients starting therapy before
the age of 6 months, 20% (4-36%) in patients starting therapy
between 6 months and 1 year, 13% (0-27%) in those starting
therapy between 1 and 1.5 years, and 0% in those who started
therapy beyond 1.5 years of age (p for trend 0.03).
Our findings confirm that age of first factor VIII administration
in children with severe hemophilia A is inversely associated with
the risk to develop antibodies against factor VIII. The role of
confounding factors such as the type of factor VIII mutation and
environmental factors needs to be evaluated.